Abstract
Stable expression of the adenovirus 5 E1A gene reduced anchorage-independent growth and tumorigenic potential, caused cytoskeletal reorganization, induced flat morphology, and restored contact inhibition in three human tumor cell lines. By these criteria, E1A appears to be functionally indistinguishable from a tumor suppressor gene in this context. The apparent paradox accorded by the observations of the ability of E1A to transform rodent cells in cooperation with other oncogenes suggests that E1A may be the prototype of a class of growth-regulatory proteins having context-specific transforming and antioncogenic activities.
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Selected References
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- Ben-Ze'ev A. The cytoskeleton in cancer cells. Biochim Biophys Acta. 1985;780(3):197–212. doi: 10.1016/0304-419x(85)90003-4. [DOI] [PubMed] [Google Scholar]
- Brunet L. J., Berk A. J. Concentration dependence of transcriptional transactivation in inducible E1A-containing human cells. Mol Cell Biol. 1988 Nov;8(11):4799–4807. doi: 10.1128/mcb.8.11.4799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Byrd P., Brown K. W., Gallimore P. H. Malignant transformation of human embryo retinoblasts by cloned adenovirus 12 DNA. Nature. 1982 Jul 1;298(5869):69–71. doi: 10.1038/298069a0. [DOI] [PubMed] [Google Scholar]
- Chen M. J., Holskin B., Strickler J., Gorniak J., Clark M. A., Johnson P. J., Mitcho M., Shalloway D. Induction by E1A oncogene expression of cellular susceptibility to lysis by TNF. Nature. 1987 Dec 10;330(6148):581–583. doi: 10.1038/330581a0. [DOI] [PubMed] [Google Scholar]
- David-Pfeuty T., Singer S. J. Altered distributions of the cytoskeletal proteins vinculin and alpha-actinin in cultured fibroblasts transformed by Rous sarcoma virus. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6687–6691. doi: 10.1073/pnas.77.11.6687. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duerksen-Hughes P., Wold W. S., Gooding L. R. Adenovirus E1A renders infected cells sensitive to cytolysis by tumor necrosis factor. J Immunol. 1989 Dec 15;143(12):4193–4200. [PubMed] [Google Scholar]
- Edelman G. M., Yahara I. Temperature-sensitive changes in surface modulating assemblies of fibroblasts transformed by mutants of Rous sarcoma virus. Proc Natl Acad Sci U S A. 1976 Jun;73(6):2047–2051. doi: 10.1073/pnas.73.6.2047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Egan C., Jelsma T. N., Howe J. A., Bayley S. T., Ferguson B., Branton P. E. Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5. Mol Cell Biol. 1988 Sep;8(9):3955–3959. doi: 10.1128/mcb.8.9.3955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Folkman J., Moscona A. Role of cell shape in growth control. Nature. 1978 Jun 1;273(5661):345–349. doi: 10.1038/273345a0. [DOI] [PubMed] [Google Scholar]
- Frisch S. M., Reich R., Collier I. E., Genrich L. T., Martin G., Goldberg G. I. Adenovirus E1A represses protease gene expression and inhibits metastasis of human tumor cells. Oncogene. 1990 Jan;5(1):75–83. [PubMed] [Google Scholar]
- Harlow E., Franza B. R., Jr, Schley C. Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products. J Virol. 1985 Sep;55(3):533–546. doi: 10.1128/jvi.55.3.533-546.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howe J. A., Mymryk J. S., Egan C., Branton P. E., Bayley S. T. Retinoblastoma growth suppressor and a 300-kDa protein appear to regulate cellular DNA synthesis. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5883–5887. doi: 10.1073/pnas.87.15.5883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsie A. W., Puck T. T. Morphological transformation of Chinese hamster cells by dibutyryl adenosine cyclic 3':5'-monophosphate and testosterone. Proc Natl Acad Sci U S A. 1971 Feb;68(2):358–361. doi: 10.1073/pnas.68.2.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levine A. J. Tumor suppressor genes. Bioessays. 1990 Feb;12(2):60–66. doi: 10.1002/bies.950120203. [DOI] [PubMed] [Google Scholar]
- Linzer D. I., Levine A. J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43–52. doi: 10.1016/0092-8674(79)90293-9. [DOI] [PubMed] [Google Scholar]
- Liu F., Green M. R. A specific member of the ATF transcription factor family can mediate transcription activation by the adenovirus E1a protein. Cell. 1990 Jun 29;61(7):1217–1224. doi: 10.1016/0092-8674(90)90686-9. [DOI] [PubMed] [Google Scholar]
- Ruley H. E. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature. 1983 Aug 18;304(5927):602–606. doi: 10.1038/304602a0. [DOI] [PubMed] [Google Scholar]
- Schreier A. A., Gruber J. Viral T-antigen interactions with cellular proto-oncogene and anti-oncogene products. J Natl Cancer Inst. 1990 Mar 7;82(5):354–360. doi: 10.1093/jnci/82.5.354. [DOI] [PubMed] [Google Scholar]
- Shin S. I., Freedman V. H., Risser R., Pollack R. Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4435–4439. doi: 10.1073/pnas.72.11.4435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tucker R. W., Sanford K. K., Handleman S. L., Jones G. M. Colony morphology and growth in agarose as tests for spontaneous neoplastic transformation in vitro. Cancer Res. 1977 May;37(5):1571–1579. [PubMed] [Google Scholar]
- Vanhaesebroeck B., Timmers H. T., Pronk G. J., van Roy F., Van der Eb A. J., Fiers W. Modulation of cellular susceptibility to the cytotoxic/cytostatic action of tumor necrosis factor by adenovirus E1 gene expression is cell type-dependent. Virology. 1990 Jun;176(2):362–368. doi: 10.1016/0042-6822(90)90006-d. [DOI] [PubMed] [Google Scholar]
- Weber K., Lazarides E., Goldman R. D., Vogel A., Pollack R. Localization and distribution of actin fibers in normal transformed and revertant cells. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 1):363–369. doi: 10.1101/sqb.1974.039.01.047. [DOI] [PubMed] [Google Scholar]
- Whyte P., Buchkovich K. J., Horowitz J. M., Friend S. H., Raybuck M., Weinberg R. A., Harlow E. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature. 1988 Jul 14;334(6178):124–129. doi: 10.1038/334124a0. [DOI] [PubMed] [Google Scholar]
- Whyte P., Williamson N. M., Harlow E. Cellular targets for transformation by the adenovirus E1A proteins. Cell. 1989 Jan 13;56(1):67–75. doi: 10.1016/0092-8674(89)90984-7. [DOI] [PubMed] [Google Scholar]
- Yu D. H., Scorsone K., Hung M. C. Adenovirus type 5 E1A gene products act as transformation suppressors of the neu oncogene. Mol Cell Biol. 1991 Mar;11(3):1745–1750. doi: 10.1128/mcb.11.3.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]